Is CFAP53 p.Arg24Ile (c.71G>T) pathogenic?

CFAP53 p.Arg24Ile (c.71G>T) is classified Likely benign in CFAP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-30). AlphaMissense: likely benign (0.2496); Rare (popmax 0.222%, amr); Associated with heterotaxy, visceral, 6, autosomal.

What condition is associated with CFAP53 p.Arg24Ile (c.71G>T)?

CFAP53 p.Arg24Ile (c.71G>T) is associated with heterotaxy, visceral, 6, autosomal (ClinVar).

How common is CFAP53 p.Arg24Ile (c.71G>T) in the general population?

CFAP53 p.Arg24Ile (c.71G>T) is rare (popmax 0.222%, amr) (gnomAD).

What do computational predictors say about CFAP53 p.Arg24Ile (c.71G>T)?

AlphaMissense predicts likely benign (score 0.2496) — an in-silico prediction, not a clinical call.

CFAP53 p.Arg24Ile

c.71G>T · rs754876515 · VCV1571589

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2496 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.222%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

heterotaxy, visceral, 6, autosomal

Computational evidence

Protein change
AlphaMissense	0.2496	likely benign
REVEL	0.219	benign-leaning
SaProt	LLR -4.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 39 kb · p 0.59 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.222% Admixed American · 133/59,912 alleles

Filtering AF 0.191% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.18%

Overall 0.00838% 135/1,610,874 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.222%	450
Remaining individualsnot grpmax-eligible	0.00321%	31,192

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CFAP53
Protein: p.Arg24Ile
Coding: c.71G>T
MANE Select: NM_145020
dbSNP: rs754876515
Type: single nucleotide variant
Location: chr18:50262218 (GRCh38)
Gene constraint: LOEUF 1.282 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.17 · 2 PDB

Full CFAP53 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

heterotaxy, visceral, 6, autosomal — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFAP53 p.Ala185Thr Uncertain significance ★★ ⚠ same condition
CFAP53 p.Ala385Ser Uncertain significance ★★ ⚠ same condition
CFAP53 p.Arg158Gly Uncertain significance ★★ ⚠ same condition
CFAP53 p.Arg257Cys Uncertain significance ★★ ⚠ same condition
CFAP53 p.Arg505His Uncertain significance ★★ ⚠ same condition
CFAP53 p.Arg505Leu Uncertain significance ★★ ⚠ same condition
CFAP53 p.Arg505Ser Uncertain significance ★★ ⚠ same condition
CFAP53 p.Asp85Asn Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cfap53-p-arg24ile (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown